Variation in upstream open reading frames contributes to allelic diversity in maize protein abundance

Joseph L. Gage, Sujina Mali, Fionn McLoughlin, Merritt Khaipho-Burch, Brandon Monier, Julia Bailey-Serres, Richard D. Vierstra, Edward S. Buckler

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The 5 untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main ORF (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans a mRNA and encounters an uORF, translation of that uORF can prevent ribosomes from reaching the mORF and cause decreased mORF translation. In this study, we first observed that rare variants in the 5 UTR dysregulate maize (Zea mays L.) protein abundance. Upon further investigation, we found that rare variants near the start codon of uORFs can repress or derepress mORF translation, causing allelic changes in protein abundance. This finding holds for common variants as well, and common variants that modify uORF start codons also contribute disproportionately to metabolic and whole-plant phenotypes, suggesting that translational regulation by uORFs serves an adaptive function. These results provide evidence for the mechanisms by which natural sequence variation modulates gene expression, and ultimately, phenotype.

Original languageEnglish
Article numbere2112516119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number14
DOIs
StatePublished - Apr 5 2022

Keywords

  • gene expression
  • maize
  • proteome
  • rare alleles
  • uORF

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